Trial Outcomes & Findings for Everolimus (RAD001) in Metastatic Transitional Cell Carcinoma of the Urothelium (NCT NCT00805129)
NCT ID: NCT00805129
Last Updated: 2022-11-25
Results Overview
To measure the two-month PFS rate of Everolimus (RAD001) as determined by RECIST. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
46 participants
Primary outcome timeframe
2 months
Results posted on
2022-11-25
Participant Flow
Participant milestones
| Measure |
Everolimus
Everolimus will be administered at a dose of 10 mg orally once daily continuously.
Everolimus: Everolimus (RAD001) is a novel oral derivative of rapamycin. Everolimus will be administered orally as a once-daily dose of 10 mg (two 5 mg tablets) continuously from study day 1 until progression of disease or unacceptable toxicity. Patients will be instructed to take Everolimus in the morning, at the same time each day. Everolimus should be taken by the patient in a fasting state or with no more than a light fat-free meal.
|
|---|---|
|
Overall Study
STARTED
|
46
|
|
Overall Study
COMPLETED
|
45
|
|
Overall Study
NOT COMPLETED
|
1
|
Reasons for withdrawal
| Measure |
Everolimus
Everolimus will be administered at a dose of 10 mg orally once daily continuously.
Everolimus: Everolimus (RAD001) is a novel oral derivative of rapamycin. Everolimus will be administered orally as a once-daily dose of 10 mg (two 5 mg tablets) continuously from study day 1 until progression of disease or unacceptable toxicity. Patients will be instructed to take Everolimus in the morning, at the same time each day. Everolimus should be taken by the patient in a fasting state or with no more than a light fat-free meal.
|
|---|---|
|
Overall Study
Not treated
|
1
|
Baseline Characteristics
Everolimus (RAD001) in Metastatic Transitional Cell Carcinoma of the Urothelium
Baseline characteristics by cohort
| Measure |
Everolimus
n=46 Participants
Everolimus will be administered at a dose of 10 mg orally once daily continuously.
Everolimus: Everolimus (RAD001) is a novel oral derivative of rapamycin. Everolimus will be administered orally as a once-daily dose of 10 mg (two 5 mg tablets) continuously from study day 1 until progression of disease or unacceptable toxicity. Patients will be instructed to take Everolimus in the morning, at the same time each day. Everolimus should be taken by the patient in a fasting state or with no more than a light fat-free meal.
|
|---|---|
|
Age, Customized
|
66 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
14 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
32 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
45 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
43 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
46 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 2 monthsTo measure the two-month PFS rate of Everolimus (RAD001) as determined by RECIST. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Outcome measures
| Measure |
Everolimus
n=45 Participants
Everolimus will be administered at a dose of 10 mg orally once daily continuously.
Everolimus: Everolimus (RAD001) is a novel oral derivative of rapamycin. Everolimus will be administered orally as a once-daily dose of 10 mg (two 5 mg tablets) continuously from study day 1 until progression of disease or unacceptable toxicity. Patients will be instructed to take Everolimus in the morning, at the same time each day. Everolimus should be taken by the patient in a fasting state or with no more than a light fat-free meal.
|
|---|---|
|
Number of Participants Who Were Progression Free at 2 Months
Progression Free
|
23 Participants
|
|
Number of Participants Who Were Progression Free at 2 Months
Not Progression Free
|
22 Participants
|
PRIMARY outcome
Timeframe: through study completion, up to 25 monthsTo determine the safety and toxicity of Everolimus (RAD001) in this patient population with toxicities being evaluated by CTCAE v3.0
Outcome measures
| Measure |
Everolimus
n=46 Participants
Everolimus will be administered at a dose of 10 mg orally once daily continuously.
Everolimus: Everolimus (RAD001) is a novel oral derivative of rapamycin. Everolimus will be administered orally as a once-daily dose of 10 mg (two 5 mg tablets) continuously from study day 1 until progression of disease or unacceptable toxicity. Patients will be instructed to take Everolimus in the morning, at the same time each day. Everolimus should be taken by the patient in a fasting state or with no more than a light fat-free meal.
|
|---|---|
|
Number of Participants Evaluated for Toxicity
|
46 Participants
|
SECONDARY outcome
Timeframe: through study completion, up to 25 monthsTo determine the response rate of Everolimus in patients with progressive urothelial cancer who have received prior cytotoxic chemotherapy using the Response Evaluation Criteria in Solid Tumors (version 1.0). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Outcome measures
| Measure |
Everolimus
n=45 Participants
Everolimus will be administered at a dose of 10 mg orally once daily continuously.
Everolimus: Everolimus (RAD001) is a novel oral derivative of rapamycin. Everolimus will be administered orally as a once-daily dose of 10 mg (two 5 mg tablets) continuously from study day 1 until progression of disease or unacceptable toxicity. Patients will be instructed to take Everolimus in the morning, at the same time each day. Everolimus should be taken by the patient in a fasting state or with no more than a light fat-free meal.
|
|---|---|
|
Response Rate
No response
|
43 Participants
|
|
Response Rate
Partial Response
|
2 Participants
|
SECONDARY outcome
Timeframe: 25 monthsTo assess markers for activated mTOR pathway (including phospho-S6 and phospho-4E BP1) in all pre-treatment tissue specimens and correlate with response to treatment and PFS.
Outcome measures
| Measure |
Everolimus
n=45 Participants
Everolimus will be administered at a dose of 10 mg orally once daily continuously.
Everolimus: Everolimus (RAD001) is a novel oral derivative of rapamycin. Everolimus will be administered orally as a once-daily dose of 10 mg (two 5 mg tablets) continuously from study day 1 until progression of disease or unacceptable toxicity. Patients will be instructed to take Everolimus in the morning, at the same time each day. Everolimus should be taken by the patient in a fasting state or with no more than a light fat-free meal.
|
|---|---|
|
Proportion of Pretreatment Primary Tumor Samples With mTOR Pathway Markers
|
0.62 Proportion of pretreatment primary tumor
|
Adverse Events
Everolimus
Serious events: 23 serious events
Other events: 39 other events
Deaths: 43 deaths
Serious adverse events
| Measure |
Everolimus
n=46 participants at risk
Everolimus will be administered at a dose of 10 mg orally once daily continuously.
Everolimus: Everolimus (RAD001) is a novel oral derivative of rapamycin. Everolimus will be administered orally as a once-daily dose of 10 mg (two 5 mg tablets) continuously from study day 1 until progression of disease or unacceptable toxicity. Patients will be instructed to take Everolimus in the morning, at the same time each day. Everolimus should be taken by the patient in a fasting state or with no more than a light fat-free meal.
|
|---|---|
|
Metabolism and nutrition disorders
Anorexia
|
2.2%
1/46 • 25 months
|
|
Cardiac disorders
Atrial tachycardia/Paroxysmal Atrial Tachycardia
|
2.2%
1/46 • 25 months
|
|
Psychiatric disorders
Confusion
|
4.3%
2/46 • 25 months
|
|
General disorders
Death not assoc w CTCAE term-Disease prog NOS
|
8.7%
4/46 • 25 months
|
|
Metabolism and nutrition disorders
Dehydration
|
4.3%
2/46 • 25 months
|
|
Gastrointestinal disorders
Diarrhea
|
2.2%
1/46 • 25 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)
|
6.5%
3/46 • 25 months
|
|
General disorders
Edema: limb
|
2.2%
1/46 • 25 months
|
|
Gastrointestinal disorders
Enteritis (inflamm of small bowel)
|
2.2%
1/46 • 25 months
|
|
General disorders
Fatigue (asthenia, lethargy, malaise)
|
4.3%
2/46 • 25 months
|
|
General disorders
Fever (in the absence of neutropenia)
|
4.3%
2/46 • 25 months
|
|
Gastrointestinal disorders
Fistula, GI- Rectum
|
2.2%
1/46 • 25 months
|
|
Injury, poisoning and procedural complications
Fracture
|
2.2%
1/46 • 25 months
|
|
Gastrointestinal disorders
Hemorrhage, Duodenum
|
2.2%
1/46 • 25 months
|
|
Renal and urinary disorders
Hemorrhage, Urinary NOS
|
2.2%
1/46 • 25 months
|
|
Infections and infestations
Inf norm ANC/gr1/2 neut-Anal/perianal
|
2.2%
1/46 • 25 months
|
|
Infections and infestations
Inf norm ANC/gr1/2 neut-Blood
|
2.2%
1/46 • 25 months
|
|
Infections and infestations
Inf norm ANC/gr1/2 neut-Bronchitis NOS
|
2.2%
1/46 • 25 months
|
|
Infections and infestations
Inf norm ANC/gr1/2 neut-Urinary(bladder)
|
2.2%
1/46 • 25 months
|
|
Infections and infestations
Inf unknown ANC-Bladder(urinary)
|
2.2%
1/46 • 25 months
|
|
Infections and infestations
Inf unknown ANC-Joint
|
4.3%
2/46 • 25 months
|
|
Infections and infestations
Inf unknown ANC-Pneumonia(lung)
|
2.2%
1/46 • 25 months
|
|
Infections and infestations
Inf unknown ANC-UTI NOS
|
4.3%
2/46 • 25 months
|
|
Investigations
Leukocytes (total WBC)
|
2.2%
1/46 • 25 months
|
|
Gastrointestinal disorders
Mucositis (Clin exam)- Oral cavity
|
2.2%
1/46 • 25 months
|
|
Musculoskeletal and connective tissue disorders
Myositis (Inflamm/damage of muscle)
|
2.2%
1/46 • 25 months
|
|
Gastrointestinal disorders
Nausea
|
4.3%
2/46 • 25 months
|
|
Gastrointestinal disorders
Obstruction, GI- Small bowel NOS
|
2.2%
1/46 • 25 months
|
|
Gastrointestinal disorders
Pain - Abdomen NOS
|
2.2%
1/46 • 25 months
|
|
Musculoskeletal and connective tissue disorders
Pain - back
|
2.2%
1/46 • 25 months
|
|
Nervous system disorders
Pain - Head/headache
|
2.2%
1/46 • 25 months
|
|
General disorders
Pain - Pain NOS
|
2.2%
1/46 • 25 months
|
|
Gastrointestinal disorders
Pancreatitis
|
2.2%
1/46 • 25 months
|
|
Metabolism and nutrition disorders
Phosphate, low (hypophosphatemia)
|
2.2%
1/46 • 25 months
|
|
Renal and urinary disorders
Renal failure
|
4.3%
2/46 • 25 months
|
|
Vascular disorders
Thrombosis/thrombus/embolism
|
4.3%
2/46 • 25 months
|
|
Cardiac disorders
Vent arrhythmia- Ventricular tachycardia
|
2.2%
1/46 • 25 months
|
|
Gastrointestinal disorders
Vomiting
|
2.2%
1/46 • 25 months
|
Other adverse events
| Measure |
Everolimus
n=46 participants at risk
Everolimus will be administered at a dose of 10 mg orally once daily continuously.
Everolimus: Everolimus (RAD001) is a novel oral derivative of rapamycin. Everolimus will be administered orally as a once-daily dose of 10 mg (two 5 mg tablets) continuously from study day 1 until progression of disease or unacceptable toxicity. Patients will be instructed to take Everolimus in the morning, at the same time each day. Everolimus should be taken by the patient in a fasting state or with no more than a light fat-free meal.
|
|---|---|
|
General disorders
Fatigue
|
84.8%
39/46 • 25 months
|
|
Investigations
Weight loss
|
63.0%
29/46 • 25 months
|
|
Gastrointestinal disorders
Mucositis
|
52.2%
24/46 • 25 months
|
|
Skin and subcutaneous tissue disorders
Rash
|
47.8%
22/46 • 25 months
|
|
Gastrointestinal disorders
Constipation
|
45.7%
21/46 • 25 months
|
|
Nervous system disorders
Neuropathy
|
45.7%
21/46 • 25 months
|
|
General disorders
Edema
|
43.5%
20/46 • 25 months
|
|
Renal and urinary disorders
Urinary frequency
|
32.6%
15/46 • 25 months
|
|
Gastrointestinal disorders
Nausea
|
30.4%
14/46 • 25 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
23.9%
11/46 • 25 months
|
|
Gastrointestinal disorders
Vomiting
|
21.7%
10/46 • 25 months
|
|
General disorders
Fever
|
19.6%
9/46 • 25 months
|
|
Gastrointestinal disorders
Diarrhea
|
15.2%
7/46 • 25 months
|
|
General disorders
Pain
|
13.0%
6/46 • 25 months
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
10.9%
5/46 • 25 months
|
|
Nervous system disorders
Dysgeusia
|
8.7%
4/46 • 25 months
|
|
Blood and lymphatic system disorders
Anemia
|
84.8%
39/46 • 25 months
|
|
Investigations
Thrombocytopenia
|
45.7%
21/46 • 25 months
|
|
Investigations
Elevated Aspartate aminotransferase
|
58.7%
27/46 • 25 months
|
|
Investigations
Elevated alanine aminotransferase
|
47.8%
22/46 • 25 months
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
58.7%
27/46 • 25 months
|
|
Metabolism and nutrition disorders
Hyponatremia
|
15.2%
7/46 • 25 months
|
|
Metabolism and nutrition disorders
Hypernatremia
|
15.2%
7/46 • 25 months
|
|
Metabolism and nutrition disorders
Hypokalemia
|
15.2%
7/46 • 25 months
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
15.2%
7/46 • 25 months
|
|
Metabolism and nutrition disorders
Hyperphosphatemia
|
34.8%
16/46 • 25 months
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
13.0%
6/46 • 25 months
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
26.1%
12/46 • 25 months
|
|
Investigations
Hypercholesterolemia
|
63.0%
29/46 • 25 months
|
|
Metabolism and nutrition disorders
Hypertriglyceridemia
|
60.9%
28/46 • 25 months
|
|
Investigations
Elevated creatinine
|
56.5%
26/46 • 25 months
|
|
Investigations
INR abnormal
|
39.1%
18/46 • 25 months
|
|
Investigations
PTT abnormal
|
26.1%
12/46 • 25 months
|
Additional Information
Dr. Dean Bajorin, MD
Memorial Sloan Kettering Cancer Center
Phone: 646-888-4700
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place